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Elife. 2017 Aug 15;6. pii: e27692. doi: 10.7554/eLife.27692.

RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system.

Author information

1
National Institute of Biological Sciences, Beijing, China.

Abstract

A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis. We report here that male reproductive organs of both Ripk3- and Mlkl-knockout mice retain 'youthful' morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. The RIPK3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild-type mice. When the testes of young wild-type mice are given a local necroptotic stimulus, their reproductive organs showed accelerated aging. Feeding of wild-type mice with an RIPK1 inhibitor prior to the normal onset of age-related changes in their reproductive organs blocked the appearance of signs of aging. Thus, necroptosis in testes promotes the aging-associated deterioration of the male reproductive system in mice.

KEYWORDS:

aging; apoptosis; cell biology; mouse; necroptosis; spermatogonia; testis

PMID:
28807105
PMCID:
PMC5557593
DOI:
10.7554/eLife.27692
[Indexed for MEDLINE]
Free PMC Article

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